Mutations in rare human diseases

Nature Genetics

August 10, 2009

Mutations in the INPP5E gene lead to defects in the primary cilium ― a microscopic antenna-like structure that protrudes from almost every cell in the mammalian body ― according to two new studies published online in this week\'s Nature Genetics. The studies report that defects in this structure lead to the genetic disorders MORM and Joubert syndrome.

Stephane Schurmans and colleagues found a mutation in INPP5E in individuals with MORM syndrome, a rare multi-organ disorder that is characterized by mental retardation, obesity, congenital retinal dystrophy and micropenis in males. Their experiments found that mutations in INPP5E led to decreased stabilization of the primary cilium, leading to multiple developmental defects.

In another study, Joseph Gleeson and colleagues discovered that other types of mutations in INPP5E lead to Joubert syndrome. This is a rare brain malformation that is characterized by the absence or underdevelopment of the cerebellar vermis, a brain region that controls balance and coordination. Common attributes of Joubert syndrome include abnormally rapid breathing, decreased muscle tone, atypical movements and mental retardation. The scientists found that the mutations in INPP5E lead to premature destabilization of primary cilia.